The rate of synthesis of a protein is determined by the rate at which the DNA encoding the protein is converted to mRNA (transcription), the steady-state amount of the active mRNA in the cell, and the rate at which the mRNA is converted into newly synthesized protein (translation). These important processes are described in detail in Chapter 5.

The life spans of intracellular proteins vary from as short as a few minutes for mitotic cyclins, which help regulate passage through the mitotic stage of cell division (see Chapter 19), to as long as the age of an organism for proteins in the lens of the eye. Protein life span is controlled primarily by regulated protein degradation.

Protein degradation plays two especially important roles in the cell. First, it removes proteins that are potentially toxic, improperly folded or assembled, or damaged—including the products of mutated genes and proteins damaged by chemically active cell metabolites or stress (e.g., heat shock). Despite the existence of chaperone-mediated protein folding, some newly made proteins are rapidly degraded because they are misfolded. This degradation might be necessary due to failure of timely engagement of the necessary chaperones to guide the folding of the proteins or due to their defective assembly into complexes. Most other proteins are degraded more slowly, undergoing about 1–2 percent degradation per hour in mammalian cells. Second, the controlled destruction of otherwise normal proteins, along with controlled rates of synthesis, provides a powerful mechanism for maintaining the appropriate levels of the proteins and their activities and for permitting rapid changes in these levels to help the cells respond to changing conditions.

Eukaryotic cells have several pathways for degrading proteins. One major pathway is degradation by enzymes within lysosomes, membrane-limited organelles whose acidic interior (pH ~4.5) is filled with a host of hydrolytic enzymes. Lysosomal degradation is directed primarily toward aged or defective organelles of the cell—a process called autophagy (see Chapter 14)—and toward extracellular proteins taken up by the cell. Lysosomes will be discussed at length in later chapters. Here we focus on another important degradation pathway: cytoplasmic protein degradation by proteasomes, which can account for up to 90 percent of the protein degradation in mammalian cells.